The mammalian intestine is colonized by trillions of microorganisms that are critical for the establishment of tissue homeostasis. Consequently, the immune system has developed strategies to maintain a mutualistic relation with the microbiota while stopping microbial spread. However, inappropriate function of the immune cells and/or alteration of the commensal composition can lead to inflammatory and autoimmune diseases, like inflammatory bowel disease.
Among the components of the intestinal immune system, NKT cells represent a predominant population with striking immune-modulatory properties. NKT cells specifically recognize and are activated by lipid antigens presented by the MHC-I-like molecule CD1. Upon antigen encounter NKT cells can induce the downstream activation of both innate (NK cells) and adaptive (B cells) immune cells. In line with the abundance and diversity of microbial-derived lipids present in the gut, numerous studies have proposed a role for NKT cells and CD1-lipid presentation in the modulation of mucosal immunity both in homeostasis and disease. However, the features of intestinal NKT cells and the mechanisms by which they exert their immunomodulatory functions remain poorly explored.
This proposal aims to unravel the cellular and molecular mechanisms that mediate the role of NKT cells in the regulation of mucosal immunity. We will use a combination of flow-cytometry, immunofluorescence and microscopy to build a comprehensive picture of NKT cell distribution and phenotype within gastro-intestinal compartments. With this established we will analyse the role of NKT cells in intestinal homeostasis by deciphering their contribution to the generation and quality of intestinal B cell responses. These studies will provide a better understanding of the factors that modulate intestinal immunity, with the potential to improve therapies for patients suffering from intestinal inflammatory diseases and possibly a broader range of disorders.
Field of science
- /natural sciences/biological sciences/biochemistry/biomolecules/lipids
- /medical and health sciences/basic medicine/physiology/homeostasis
- /medical and health sciences/health sciences/inflammatory diseases
- /medical and health sciences/basic medicine/immunology
- /medical and health sciences/clinical medicine/gastroenterology/inflammatory bowel disease
Call for proposal
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